α
2-Macroglobulin (α
2M), or alpha-2-macroglobulin, is a large (720 KDa)
plasma protein found in the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...
. It is mainly produced by the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
, and also locally synthesized by
macrophages,
fibroblasts, and
adrenocortical cells
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It i ...
. In humans it is encoded by the ''A2M'' gene.
α
2-Macroglobulin acts as an antiprotease and is able to inactivate an enormous variety of proteinases. It functions as an inhibitor of fibrinolysis by inhibiting
plasmin and
kallikrein. It functions as an inhibitor of coagulation by inhibiting
thrombin. α
2-macroglobulin may act as a carrier protein because it also binds to numerous growth factors and cytokines, such as platelet-derived growth factor, basic fibroblast growth factor, TGF-β, insulin, and IL-1β.
No specific deficiency with associated disease has been recognized, and no disease state is attributed to low concentrations of α
2-macroglobulin. The concentration of α
2-macroglobulin rises 10-fold or more in the nephrotic syndrome when other lower molecular weight proteins are lost in the urine. The loss of α
2-macroglobulin into urine is prevented by its large size. The net result is that α
2-macroglobulin reaches serum levels equal to or greater than those of albumin in the nephrotic syndrome, which has the effect of maintaining
oncotic pressure.
Structure
Human α
2-macroglobulin is composed of four identical subunits bound together by
-S-S- bonds.
In addition to
tetrameric forms of α
2-macroglobulin,